CMN Weekly (9 December 2022) - Your Weekly CRISPR Medicine News

Some of the best links we picked up around the internet

By: Gorm Palmgren - Dec. 9, 2022

Jennifer Doudna and colleagues describe a simple strategy to influence DNA repair pathway choice and improve HDR efficiency by decorating chromatin with engineered CRISPR-Cas9-methyltransferase fusion proteins. This strategy highlights the impact of histone modifications on DNA repair following CRISPR-Cas-induced double-stranded breaks and adds to the CRISPR genome editing toolbox.
South China Morning Post reports that He Jiankui - the Chinese scientist behind gene-edited babies - will discuss the ethics of his research in a series of public talks in March at Oxford University. He was released from prison earlier this year and is now looking at how CRISPR technology can help treat genetic diseases.

British researchers have investigated how primary chromatin structure and epigenetics may influence off-target activity in CRISPR-Cas9 genome editing. They publish an off-target dataset containing 19 epigenetic features. The authors believe it will help the CRISPR-Cas9 community understand the relationship between epigenetic markers and CRISPR-Cas9 off-target activity.
Researchers in Denmark have developed a method for multiparametric and accurate functional analysis of genetic sequence variants using CRISPR-Select. It is a set of flexible knock-in assays that introduce a genetic variant in a cell population and track its absolute frequencies relative to an internal, neutral control mutation as a function of time, space or a cell state measurable by flow cytometry.
American researchers have explored the feasibility of adenine base editing (ABE)-mediated exon skipping as a therapeutic strategy for Duchenne muscular dystrophy (DMD). In a DMD hiPSC cell model, they demonstrated that transfection of an ABE and a gRNA targeting the splice acceptor led to efficient conversion of AG to GG (35.9 ± 5.7%) and enabled exon 55 skipping. Furthermore, complete AG to GG conversion in a single clone restored dystrophin expression (42.5 ± 11.0% of WT).

Preliminary results from Vor Biopharma reported that the first patient given its gene editing therapy for acute myeloid leukaemia (AML) is in remission. The medication is called trem-cel (formerly VOR33) and uses CRISPR-Cas9 in blood cells to knock out CD33, thereby making them resistant to the CD33-targeted therapy Mylotarg.
Editas Medicine announced positive initial clinical data from the first two patients with sickle cell disease (SCD) treated with EDIT-301 in the Phase 1/2 RUBY trial. EDIT-301 uses AsCas12a, a novel, proprietary, highly efficient, and specific gene editing nuclease, to edit the promoter regions of gamma-globin gene 1 and 2 to increase the expression of HbF to mimic the natural mechanism of hereditary persistence of fetal haemoglobin to treat SCD.
Poseida Therapeutics presented early clinical results from its Phase 1 clinical trials of P-MUC1C-ALLO1 and P-BCMA-ALLO1 - two gene-edited allogeneic cell therapies for solid tumours and relapsed/refractory multiple myeloma, respectively - at the recent ESMO I-O 2022 Annual Congress.
Beam Therapeutics announced that FDA had lifted the clinical hold on its IND application for BEAM-201. The multiplex base-edited T-cell therapy BEAM-201 has been developed to treat relapsed/refractory T-cell acute lymphoblastic leukaemia (T-ALL)/T-cell lymphoblastic lymphoma (T-LL).

A novel ultrasensitive sensor for detecting microRNAs is based on CRISPR-Cas12a and click chemistry-terminal deoxynucleotidyl transferase (ccTdT) for signal amplification. The sensor has a broad linear detection range, from 1 pM to 10⁵ pM, with detection limits as low as 88 fM under optimal experimental conditions.
Monkeypox virus can now be detected with the naked eye with a portable CRISPR-Cas-based system. The system harnesses the high selectivity of CRISPR-Cas12 and the isothermal nucleic acid amplification potential of recombinase polymerase amplification (RPA).
Chinese researchers have developed a one-step CRISPR-Cas12a-mediated isothermal amplification for rapid and high-resolution digital detection of rare mutant alleles. CRISPR ASsoaciated Mutation Allele Rapid Test (CASMART) is an alternative to conventional single nucleotide polymorphism detection methods.
Chinese researchers report on a method for the rapid and unamplified detection of SARS-CoV-2 RNA via CRISPR-Cas13a-modified solution-gated graphene transistors. Using the gene-targeting capacity of CRISPR-Cas13a and gate functionalization via multilayer modification, SARS-CoV-2 nucleic acid sequences can be quickly and precisely identified without the need for amplification or fluorescence tagging.

Taiwan researchers look at nanoparticle-mediated CRISPR-Cas9 gene therapy in inherited retinal diseases. The review highlights important advances in nanoparticle-based gene therapy, the CRISPR-Cas9 system, and iPSC-derived retinal organoids focusing on IRDs.
A review by Chinese researchers highlights the recent development of CRISPR/Cas-based biosensors for miRNA detection. We summarize these miRNA biosensors' principles, features, and performance and highlight the remaining challenges and future directions.
A Pakistan researchers review discusses the genome editing strategies and potential applications of prime editing for treating β-thalassemia. In addition, the review also focuses on challenges associated with the use of prime editing.

This week's clinical update looked at the latest clinical data from Editas Medicine's ongoing RUBY trial for EDIT-301 in severe sickle cell disease. It also brought updates about Caribou Biosciences' PD-1 knockout CAR-T cell therapeutic candidate for relapsed or refractory large B cell lymphoma and non-Hodgkin lymphoma.

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